This work involves the development of a new facile procedure for isolation of cell surface proteins as well as facile methods for identifying proteins unique to the surface of transformed cells. Our proposed procedure for the isolation of cell surface protein involves synthesis of macromolecular reagents consisting of a) a reactive group capable of forming a specific covalent bond with proteins; b) a macromolecular carrier, and c) a linkage between the two that is stable under normal physiological conditions, but may be selectively broken. The reactive group can be designed with many variations in specificity. Reagents directed toward thiol groups, amino groups, are being studied at this time. Proteins released from the resin will be further purified by electrophoresis and ion exchange chromatography. Reactions of iodoacetate and the interactions of trypsin with 3T3 cells are also being studied with the goal of gaining further information concerning protein-protein interactions in membranes and the nature of interactions of trypsin with cells that cause this enzyme to be mitogenic.